Structure of 468075-00-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
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| CAS No. : | 468075-00-5 |
| Formula : | C7H3BrClF3O |
| M.W : | 275.45 |
| SMILES Code : | FC(F)(F)OC1=CC=C(Cl)C(Br)=C1 |
| English Name : | 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene |
| MDL No. : | MFCD06797751 |
| InChI Key : | LTBFNTUNLKPFPI-UHFFFAOYSA-N |
| Pubchem ID : | 2761405 |
| Num. heavy atoms | 13 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.14 |
| Num. rotatable bonds | 2 |
| Num. H-bond acceptors | 4.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 45.84 |
| TPSA ? Topological Polar Surface Area: Calculated from |
9.23 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.52 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.37 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.26 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.59 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.73 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.9 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-4.51 |
| Solubility | 0.0085 mg/ml ; 0.0000309 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-4.28 |
| Solubility | 0.0145 mg/ml ; 0.0000525 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.49 |
| Solubility | 0.00889 mg/ml ; 0.0000323 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.88 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.8 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With hydrogenchloride; copper(II) chloride In acetonitrile at 20℃; for 1h; | 25 DESCRIPTION 25.2-Bromo-1-chloro-4-(trifluoromethoxy)benzene To anhydrous copper [(II)] chloride (6.3g, 47mmol) in acetonitrile (lOOmL) was added tert-butyl nitrite (6.85mL, [58MMOL),] followed dropwise by a solution of [2-BROMO-4- (TRIFLUOROMETHOXY)] aniline (lOg, 39mmol) in acetonitrile [(15ML).] The solution was stirred at ambient temperature for 1 hour then poured into hydrochloric acid (250mL, 2M). The suspension formed was extracted with diethyl ether [(2X250ML)] and the extracts were dried [(MGS04).] Concentration yielded the title compound as an oil (7.82g, [28MMOL).] [ON] (360 MHz, [CDCL3)] : 7.51 [(1H,] d, J 3.2Hz), 7.48 [(1H,] d, J 8.8Hz), 7.15 [(1H,] dd, J 3.2 and 8.8Hz). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: 2-bromo-1-chloro-4-(trifluoromethoxy)benzene; tri-n-butylvinyl tin In toluene for 0.75h; Stage #2: for 2h; Heating / reflux; | 26 DESCRIPTION 26.1-Chloro-2-vinyl-4-(trifluoromethoxy)benzene (Description 25; [L.] [OG,] 3.6mmol) and tri-n-butylvinyl tin (1.21g, 3. [8MMOL)] were dissolved in toluene (20mL) and the solution was degassed for 45 minutes with nitrogen. Tetrakis (triphenylphosphine) palladium [(0)] (lOOmg) was then added and the solution heated at reflux for 2 hours. Once cooled, the solution was concentrated and the residue was purified by silica chromatography to give the title compound [(274MG,] [1.] [2MMOL).] [ON] (360 MHz, [CDCL3)] : 7.40-7. 36 (2H, m), 7.09-7. 01 (2H, m), 5.75 [(1H,] d, J 17.5Hz), 5.47 [(1H,] d, J [10.] 9Hz). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: 2-bromo-1-chloro-4-(trifluoromethoxy)benzene With tert.-butyl lithium In tetrahydrofuran; pentanes at -78℃; Stage #2: tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate In tetrahydrofuran; pentanes at 20℃; | 16.1 INTERMEDIATE 16; [2-Cyclopropyl-5-(trifluoromethoxy)phenyl1(piperidin-4-yl)methanone hydrochloride; Step 1 : /erf -Butyl -4- { [2-chloro-5 -(trifluoromethoxy)phenyl] carbonyl 1 piperidine- 1 carboxvlate; To a -78 C solution of 2-bromo-l-chloro-4-(trifluoromethoxy)benzene (2.95 g, 10.7 mmol) in THF (55 mL) was slowly added teλt-butyllithium (1.7 M in pentanes, 12.6 niL, 21.4 mmol). After stirring at -78 C for a few minutes, a solution of tert-butyl-4- (methoxy(methyl)carbamoyl)piperidine-l-carboxylate (2.65 g, 9.73 mmol) in THF (2 mL) was added to the reaction mixture. At the end of the addition, the cold bath was removed and the reaction mixture was warmed to room temperature and stirred at this temperature for 1 h. The reaction mixture was re-cooled to -10 C and quenched with a saturated solution of ammonium chloride. The mixture was poured into a separatory funnel and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent removed under reduced pressure. Purification by column chromatography through silica gel, eluting with 2% EtOAc in hexanes to 30% EtOAc in hexanes as a gradient, afforded the title compound. | |
| With tert.-butyl lithium In tetrahydrofuran; pentane at -78 - 20℃; | 16.1 Step 1: tert-Butyl-4-[2-chloro-5-(trifluoromethoxy)phenyl]carbonyl}piperidine-1-carboxylate To a -78° C. solution of 2-bromo-1-chloro-4-(trifluoromethoxy)benzene (2.95 g, 10.7 mmol) in THF (55 mL) was slowly added tert-butyllithium (1.7 M in pentanes, 12.6 mL, 21.4 mmol). After stirring at -78° C. for a few minutes, a solution of tert-butyl-4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (2.65 g, 9.73 mmol) in THF (2 mL) was added to the reaction mixture. At the end of the addition, the cold bath was removed and the reaction mixture was warmed to room temperature and stirred at this temperature for 1 h. The reaction mixture was re-cooled to -10° C. and quenched with a saturated solution of ammonium chloride. The mixture was poured into a separatory funnel and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent removed under reduced pressure. Purification by column chromatography through silica gel, eluting with 2% EtOAc in hexanes to 30% EtOAc in hexanes as a gradient, afforded the title compound. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 83% | With 2-Picolinic acid; potassium phosphate; copper(l) iodide In dimethyl sulfoxide at 110℃; for 24h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | With tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl-(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine; potassium carbonate In <i>tert</i>-butyl alcohol at 100℃; for 5h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 88% | With tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl-(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine; potassium carbonate In <i>tert</i>-butyl alcohol at 100℃; for 5h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: tert.-butyl lithium / pentane; tetrahydrofuran / -78 - 20 °C 2: potassium phosphate; palladium diacetate / tricyclohexylphosphine / ethyl acetate; toluene; water; tetrahydrofuran / 24 h / 80 °C / Inert atmosphere |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: tert.-butyl lithium / pentane; tetrahydrofuran / -78 - 20 °C 2: potassium phosphate; palladium diacetate / tricyclohexylphosphine / ethyl acetate; toluene; water; tetrahydrofuran / 24 h / 80 °C / Inert atmosphere 3: hydrogenchloride / 1,4-dioxane / 17 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 115 - 120℃; for 16h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine / 2585.81 Torr 2: sodium tetrahydroborate; methanol / tetrahydrofuran / 2.25 h / 70 °C | ||
| Multi-step reaction with 2 steps 1: triethylamine; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / ethanol / 16 h / 80 °C / 2585.81 Torr 2: lithium aluminium tetrahydride / 1 h / -40 °C | ||
| Multi-step reaction with 2 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine / 16 h / 80 °C / 2585.81 Torr 2: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / -40 °C |
| Multi-step reaction with 2 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine / 16 h / 80 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / -40 °C | ||
| Multi-step reaction with 2 steps 1: triethylamine; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 16 h / 80 °C / 2585.81 Torr 2: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / -40 °C |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine / 2585.81 Torr 2: sodium tetrahydroborate; methanol / tetrahydrofuran / 2.25 h / 70 °C 3: sulfuric acid; bromine; silver sulfate / water / 1 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine / 2585.81 Torr 2: sodium tetrahydroborate; methanol / tetrahydrofuran / 2.25 h / 70 °C 3: sulfuric acid; bromine; silver sulfate / water / 1 h / 20 °C 4: tert.-butylhydroperoxide; potassium iodide / 48 h / Reflux |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 6 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine / 2585.81 Torr 2: sodium tetrahydroborate; methanol / tetrahydrofuran / 2.25 h / 70 °C 3: sulfuric acid; bromine; silver sulfate / water / 1 h / 20 °C 4: tert.-butylhydroperoxide; potassium iodide / 48 h / Reflux 5: water; lithium hydroxide / methanol / 1 h / 60 °C 6: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 9 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine / 2585.81 Torr 2: sodium tetrahydroborate; methanol / tetrahydrofuran / 2.25 h / 70 °C 3: sulfuric acid; bromine; silver sulfate / water / 1 h / 20 °C 4: tert.-butylhydroperoxide; potassium iodide / 48 h / Reflux 5: water; lithium hydroxide / methanol / 1 h / 60 °C 6: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 20 °C 7: potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; toluene / 90 °C / Inert atmosphere; Sealed tube 8: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C 9: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C |

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